DESCRIPTION (Abstract of the application) The objectives of the Beaumont/Henry Ford interstitial cystitis (IC) clinical center are (1) to provide an experienced clinical center that will collaborate with the other IC centers and the data coordinating center to conduct clinical trials for treating patients with IC, (2) to conduct a prospective randomized placebo controlled trial comparing intravesical BCG in patients with IC pretreated with intravesical pentosan Polysulfate (PPS) or placebo, (3) to perform a preliminary (pilot) study to reinduce IC patients who failed the initial intravesical BCG therapy with a second induction of intravesical BCG. The first clinical trial will test the hypothesis that pretreatment of the bladder with intravesical PPS prior to instillation of BCG will increase the response rate compared to intravesical BCG alone. The enhancing effect of PPS on intravesical BCG treatment is believed to be due to strong attachment of BC to PPS, which binds tightly to the bladder mucosal lining. By increasing the binding of BCG to the bladder, we hypothesize that the immunologic effect of BCG may be enhanced. The second clinical trail will test the hypothesis that re-induction of intravesical BCG therapy to BCG non-responders will convert 50 of these to responders, similar to the response rate of carcinoma-in-situ patients who receive a reinduction BCG therapy. It is assumed that the second therapy will enhance the initial immunity conferred to these non-responders. The Beaumont/Henry Ford center will provide the NIH trial group a team of investigators experienced in clinical collaborative research as they have been part of the IC Data Base with a proven record of successful recruitment and retention of IC subjects. The team has expertise in clinical trials specifically in the use of BCG in the treatment of IC. If the proposed trials prove to be successful, we will be armed with a highly effective and durable treatment for IC. The combination therapy will also potentially reduce the dos of BCG, which will lower the cost and decrease the potential morbidity of this treatment program.